一项揭示中国红霉素耐药携带等位基因出现情况的横断面研究。
A Cross-Sectional Study Revealing the Emergence of Erythromycin-Resistant Carrying Alleles in China.
作者信息
Wu Xiaoying, Du Qianqian, Li Dongfang, Yuan Lin, Meng Qinghong, Fu Zhou, Xu Hongmei, Yao Kaihu, Zhao Ruiqiu
机构信息
Department of Infectious Diseases, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China.
Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
出版信息
Front Microbiol. 2022 Jul 18;13:901617. doi: 10.3389/fmicb.2022.901617. eCollection 2022.
BACKGROUND
Previous limited studies have identified that isolates circulating in China possess distinct molecular features and high rates of erythromycin-resistance (ER). Their evolution and potential impact on the prevention and control of global pertussis are worthy of attention.
METHODS
The present cross-sectional study involved 311 non-duplicate and unrelated strains isolated from Chinese children from 2017 to 2019. Their antimicrobial susceptibilities were assessed using both -test strips and Kirby-Bauer (KB) disk diffusion methods. Seven virulence-related genes (, , , , , , and ) and the A2047G mutation in the 23S rRNA gene were detected by PCR. Based on the susceptibilities and genotypes, 50 isolates were selected for multi-locus variable-number tandem-repeat analysis (MLVA) typing and whole-genome sequencing.
RESULTS
A total of 311 strains were isolated from children with a median age of 4 months (interquartile range: 2-9 months). Strains carrying the allele were more frequent (84.9%, 264/311), were always ER (except for one strain), and were mainly related to alleles (99.6%, 263/264). The remaining 47 (15.1%) strains carried the allele, mainly harboring the alleles (93.6%, 44/47), and were sensitive to erythromycin (except for two strains). The two ER- isolates were first identified in China, belonged to MT27 and MT28 according to MLVA, and were classified into sub-lineage IVd by phylogenetic analysis of their genome sequences. This sub-lineage also includes many strains carrying the allele spreading in developed countries. For each tested antimicrobial, the susceptibilities judged by KB disks were consistent with those determined by -test strips.
CONCLUSION
The present results reveal that strains with the -ER profile still dominate in China, and a few strains carrying the allele have acquired the A2047G mutation in the 23S rRNA gene and the ER phenotype. The surveillance of the drug susceptibility of is necessary for all countries, and the KB disk method can be adopted as a screening test.
背景
先前有限的研究已确定，在中国传播的分离株具有独特的分子特征和较高的红霉素耐药率（ER）。它们的进化及其对全球百日咳预防和控制的潜在影响值得关注。
方法
本横断面研究纳入了2017年至2019年从中国儿童中分离出的311株非重复且不相关的菌株。使用Etest试纸条和 Kirby-Bauer（KB）纸片扩散法评估它们的抗菌药物敏感性。通过聚合酶链反应（PCR）检测7个与毒力相关的基因（，，，，，，和）以及23S rRNA基因中的A2047G突变。根据药敏结果和基因型，选择50株分离株进行多位点可变数目串联重复序列分析（MLVA）分型和全基因组测序。
结果
共从年龄中位数为4个月（四分位间距：2 - 9个月）的儿童中分离出311株百日咳杆菌菌株。携带等位基因的菌株更为常见（84.9%，264/311），始终对红霉素耐药（除一株外），且主要与等位基因相关（99.6%，263/264）。其余47株（15.1%）携带等位基因，主要含有等位基因（93.6%，44/47），并且对红霉素敏感（除两株外）。这两株红霉素耐药分离株首次在中国被鉴定出来，根据MLVA属于MT27和MT28，通过对其基因组序列进行系统发育分析被归类为IVd亚系。该亚系还包括许多在发达国家传播的携带等位基因的菌株。对于每种测试的抗菌药物，KB纸片法判断的药敏结果与Etest试纸条法确定的结果一致。
结论
目前的结果表明，具有-ER表型的百日咳杆菌菌株在中国仍然占主导地位，少数携带等位基因的菌株在23S rRNA基因中获得了A2047G突变并呈现红霉素耐药表型。各国均有必要对百日咳杆菌进行药敏监测，KB纸片法可作为筛查试验采用。
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